CA2861643C - Methods of reducing risk of cardiovascular disease - Google Patents
Methods of reducing risk of cardiovascular disease Download PDFInfo
- Publication number
- CA2861643C CA2861643C CA2861643A CA2861643A CA2861643C CA 2861643 C CA2861643 C CA 2861643C CA 2861643 A CA2861643 A CA 2861643A CA 2861643 A CA2861643 A CA 2861643A CA 2861643 C CA2861643 C CA 2861643C
- Authority
- CA
- Canada
- Prior art keywords
- patient
- compound
- ldl
- statin
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000000034 method Methods 0.000 title abstract description 85
- 208000024172 Cardiovascular disease Diseases 0.000 title description 22
- 108010028554 LDL Cholesterol Proteins 0.000 claims abstract description 146
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims abstract description 117
- 238000011282 treatment Methods 0.000 claims abstract description 66
- 230000007211 cardiovascular event Effects 0.000 claims abstract description 60
- 208000029078 coronary artery disease Diseases 0.000 claims abstract description 57
- 230000000306 recurrent effect Effects 0.000 claims abstract description 30
- 230000003247 decreasing effect Effects 0.000 claims abstract description 27
- 150000001875 compounds Chemical class 0.000 claims description 162
- SDMBRCRVFFHJKR-UHFFFAOYSA-N 6-(5-carboxy-5-methylhexoxy)-2,2-dimethylhexanoic acid Chemical compound OC(=O)C(C)(C)CCCCOCCCCC(C)(C)C(O)=O SDMBRCRVFFHJKR-UHFFFAOYSA-N 0.000 claims description 80
- 229950004781 gemcabene Drugs 0.000 claims description 76
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 75
- 150000003839 salts Chemical class 0.000 claims description 50
- 239000000203 mixture Substances 0.000 claims description 27
- 235000012000 cholesterol Nutrition 0.000 claims description 25
- 150000002148 esters Chemical class 0.000 claims description 25
- 230000002829 reductive effect Effects 0.000 claims description 13
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 12
- 159000000007 calcium salts Chemical class 0.000 claims description 12
- 150000003626 triacylglycerols Chemical class 0.000 claims description 12
- 206010012601 diabetes mellitus Diseases 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 9
- 239000003112 inhibitor Substances 0.000 claims description 9
- 229940122392 PCSK9 inhibitor Drugs 0.000 claims description 7
- 229920000080 bile acid sequestrant Polymers 0.000 claims description 7
- 239000008280 blood Substances 0.000 claims description 7
- 210000004369 blood Anatomy 0.000 claims description 7
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 6
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 6
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 claims description 6
- 229960005370 atorvastatin Drugs 0.000 claims description 6
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 claims description 5
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 5
- 239000003529 anticholesteremic agent Substances 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 claims description 5
- 229940125881 cholesteryl ester transfer protein inhibitor Drugs 0.000 claims description 5
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 claims description 5
- 229960003765 fluvastatin Drugs 0.000 claims description 5
- 229960004844 lovastatin Drugs 0.000 claims description 5
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 5
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 5
- 230000000391 smoking effect Effects 0.000 claims description 5
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- 101150102415 Apob gene Proteins 0.000 claims description 4
- 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 claims description 4
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 4
- -1 cholestryamine Chemical compound 0.000 claims description 4
- 229960000815 ezetimibe Drugs 0.000 claims description 4
- 108010038232 microsomal triglyceride transfer protein Proteins 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 230000002028 premature Effects 0.000 claims description 4
- 229940121649 protein inhibitor Drugs 0.000 claims description 4
- 239000012268 protein inhibitor Substances 0.000 claims description 4
- 229960002855 simvastatin Drugs 0.000 claims description 4
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 4
- 239000004059 squalene synthase inhibitor Substances 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 3
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 3
- 229940127088 antihypertensive drug Drugs 0.000 claims description 3
- 230000002490 cerebral effect Effects 0.000 claims description 3
- 229960002797 pitavastatin Drugs 0.000 claims description 3
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 claims description 3
- 229960002965 pravastatin Drugs 0.000 claims description 3
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 3
- 229960000672 rosuvastatin Drugs 0.000 claims description 3
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims description 3
- 230000006441 vascular event Effects 0.000 claims description 2
- 229940009349 vytorin Drugs 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 2
- PNAMDJVUJCJOIX-XVZWKFLSSA-N vytorin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1.N1([C@@H]([C@H](C1=O)CC[C@@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 PNAMDJVUJCJOIX-XVZWKFLSSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 description 22
- 238000001727 in vivo Methods 0.000 description 19
- 239000002243 precursor Substances 0.000 description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- 125000000217 alkyl group Chemical group 0.000 description 15
- 108010010234 HDL Lipoproteins Proteins 0.000 description 14
- 102000015779 HDL Lipoproteins Human genes 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 12
- 125000002837 carbocyclic group Chemical group 0.000 description 12
- 229910052799 carbon Inorganic materials 0.000 description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 11
- 230000009467 reduction Effects 0.000 description 11
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 150000002632 lipids Chemical class 0.000 description 10
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
- 108010023302 HDL Cholesterol Proteins 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 101150092476 ABCA1 gene Proteins 0.000 description 7
- 102000055510 ATP Binding Cassette Transporter 1 Human genes 0.000 description 7
- 108700005241 ATP Binding Cassette Transporter 1 Proteins 0.000 description 7
- 239000000902 placebo Substances 0.000 description 7
- 229940068196 placebo Drugs 0.000 description 7
- 238000008214 LDL Cholesterol Methods 0.000 description 6
- 208000001145 Metabolic Syndrome Diseases 0.000 description 6
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 6
- HYHMLYSLQUKXKP-UHFFFAOYSA-N bempedoic acid Chemical compound OC(=O)C(C)(C)CCCCCC(O)CCCCCC(C)(C)C(O)=O HYHMLYSLQUKXKP-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 102000004895 Lipoproteins Human genes 0.000 description 5
- 108090001030 Lipoproteins Proteins 0.000 description 5
- 108091081013 MiR-33 Proteins 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 230000002526 effect on cardiovascular system Effects 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 5
- 108010007622 LDL Lipoproteins Proteins 0.000 description 4
- 102000007330 LDL Lipoproteins Human genes 0.000 description 4
- 108700011259 MicroRNAs Proteins 0.000 description 4
- 108010069201 VLDL Cholesterol Proteins 0.000 description 4
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 230000003143 atherosclerotic effect Effects 0.000 description 4
- 208000019622 heart disease Diseases 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 208000010125 myocardial infarction Diseases 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 230000035488 systolic blood pressure Effects 0.000 description 4
- 150000003536 tetrazoles Chemical class 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 108010004103 Chylomicrons Proteins 0.000 description 3
- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 description 3
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 229960002297 fenofibrate Drugs 0.000 description 3
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000009097 single-agent therapy Methods 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 2
- 108010082126 Alanine transaminase Proteins 0.000 description 2
- 108010008150 Apolipoprotein B-100 Proteins 0.000 description 2
- 102000006991 Apolipoprotein B-100 Human genes 0.000 description 2
- 208000014882 Carotid artery disease Diseases 0.000 description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 description 2
- 208000005764 Peripheral Arterial Disease Diseases 0.000 description 2
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 2
- 208000007814 Unstable Angina Diseases 0.000 description 2
- PNAMDJVUJCJOIX-IUNFJCKHSA-N [(1s,3r,7s,8s,8ar)-8-[2-[(2r,4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] 2,2-dimethylbutanoate;(3r,4s)-1-(4-fluorophenyl)-3-[(3s)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1.N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 PNAMDJVUJCJOIX-IUNFJCKHSA-N 0.000 description 2
- 208000002223 abdominal aortic aneurysm Diseases 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 239000003524 antilipemic agent Substances 0.000 description 2
- 208000007474 aortic aneurysm Diseases 0.000 description 2
- 229960000516 bezafibrate Drugs 0.000 description 2
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 2
- 229940096699 bile acid sequestrants Drugs 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000035487 diastolic blood pressure Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000000260 hypercholesteremic effect Effects 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 239000002679 microRNA Substances 0.000 description 2
- 238000007427 paired t-test Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000001124 posttranscriptional effect Effects 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- BPPVUXSMLBXYGG-UHFFFAOYSA-N 4-[3-(4,5-dihydro-1,2-oxazol-3-yl)-2-methyl-4-methylsulfonylbenzoyl]-2-methyl-1h-pyrazol-3-one Chemical compound CC1=C(C(=O)C=2C(N(C)NC=2)=O)C=CC(S(C)(=O)=O)=C1C1=NOCC1 BPPVUXSMLBXYGG-UHFFFAOYSA-N 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 101800001976 Apolipoprotein B-48 Proteins 0.000 description 1
- 102400000352 Apolipoprotein B-48 Human genes 0.000 description 1
- 108010071619 Apolipoproteins Proteins 0.000 description 1
- 102000007592 Apolipoproteins Human genes 0.000 description 1
- 229920001268 Cholestyramine Polymers 0.000 description 1
- 241001091551 Clio Species 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
- 208000030673 Homozygous familial hypercholesterolemia Diseases 0.000 description 1
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 1
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 101000668058 Infectious salmon anemia virus (isolate Atlantic salmon/Norway/810/9/99) RNA-directed RNA polymerase catalytic subunit Proteins 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- 108010003718 LDL-Receptor Related Protein-Associated Protein Proteins 0.000 description 1
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 235000014435 Mentha Nutrition 0.000 description 1
- 241001072983 Mentha Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 229940127355 PCSK9 Inhibitors Drugs 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000007718 Stable Angina Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000001163 Tangier disease Diseases 0.000 description 1
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 1
- 238000001793 Wilcoxon signed-rank test Methods 0.000 description 1
- 208000004622 abetalipoproteinemia Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 235000015241 bacon Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 201000001883 cholelithiasis Diseases 0.000 description 1
- 230000001906 cholesterol absorption Effects 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000013367 dietary fats Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000001842 enterocyte Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229960002027 evolocumab Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000004129 fatty acid metabolism Effects 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 208000020694 gallbladder disease Diseases 0.000 description 1
- 208000001130 gallstones Diseases 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229960003627 gemfibrozil Drugs 0.000 description 1
- 230000008571 general function Effects 0.000 description 1
- 208000027700 hepatic dysfunction Diseases 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 108010022197 lipoprotein cholesterol Proteins 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000003228 microsomal effect Effects 0.000 description 1
- 235000014569 mints Nutrition 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 102000042567 non-coding RNA Human genes 0.000 description 1
- 108091027963 non-coding RNA Proteins 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000009038 pharmacological inhibition Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002924 silencing RNA Substances 0.000 description 1
- 229940074790 simvastatin and ezetimibe Drugs 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000010009 steroidogenesis Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 229940051223 zetia Drugs 0.000 description 1
- 238000011680 zucker rat Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261584002P | 2012-01-06 | 2012-01-06 | |
| US61/584,002 | 2012-01-06 | ||
| PCT/US2013/020317 WO2013103842A1 (en) | 2012-01-06 | 2013-01-04 | Methods of reducing risk of cardiovascular disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2861643A1 CA2861643A1 (en) | 2013-07-11 |
| CA2861643C true CA2861643C (en) | 2020-10-06 |
Family
ID=48745439
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2861643A Active CA2861643C (en) | 2012-01-06 | 2013-01-04 | Methods of reducing risk of cardiovascular disease |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US10028926B2 (enExample) |
| EP (2) | EP2800564B1 (enExample) |
| JP (2) | JP6295205B2 (enExample) |
| CN (2) | CN110025608A (enExample) |
| AU (1) | AU2013207423B2 (enExample) |
| CA (1) | CA2861643C (enExample) |
| HK (1) | HK1201452A1 (enExample) |
| MX (1) | MX367352B (enExample) |
| WO (1) | WO2013103842A1 (enExample) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3578205A1 (en) | 2010-08-06 | 2019-12-11 | ModernaTX, Inc. | A pharmaceutical formulation comprising engineered nucleic acids and medical use thereof |
| HUE069586T2 (hu) | 2010-10-01 | 2025-03-28 | Modernatx Inc | Módosított nukleozidok, nukleotidok és nukleinsavak, valamint ezek felhasználása |
| JP2014511687A (ja) | 2011-03-31 | 2014-05-19 | モデルナ セラピューティクス インコーポレイテッド | 工学操作された核酸の送達および製剤 |
| US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| DK3682905T3 (da) | 2011-10-03 | 2022-02-28 | Modernatx Inc | Modificerede nukleosider, nukleotider og nukleinsyrer og anvendelser deraf |
| HRP20220717T1 (hr) | 2011-12-16 | 2022-07-22 | Modernatx, Inc. | Modificirani pripravci mrna |
| US9440754B2 (en) | 2012-03-29 | 2016-09-13 | R.P. Scherer Technologies, Llc | Three circuit fill system for blow fill seal containers |
| US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
| US10501512B2 (en) | 2012-04-02 | 2019-12-10 | Modernatx, Inc. | Modified polynucleotides |
| US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
| JP6189415B2 (ja) | 2012-04-02 | 2017-08-30 | モデルナティエックス インコーポレイテッドＭｏｄｅｒｎａＴＸ，Ｉｎｃ． | 細胞質および細胞骨格タンパク質の産生のための修飾ポリヌクレオチド |
| US9255154B2 (en) | 2012-05-08 | 2016-02-09 | Alderbio Holdings, Llc | Anti-PCSK9 antibodies and use thereof |
| EP2922554B1 (en) | 2012-11-26 | 2022-02-23 | ModernaTX, Inc. | Terminally modified rna |
| US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
| KR101695582B1 (ko) | 2013-04-17 | 2017-01-13 | 화이자 인코포레이티드 | 심혈관 질환을 치료하기 위한 n-피페리딘-3-일벤즈아미드 유도체 |
| KR20160067219A (ko) | 2013-10-03 | 2016-06-13 | 모더나 세라퓨틱스, 인코포레이티드 | 저밀도 지단백질 수용체를 암호화하는 폴리뉴클레오타이드 |
| EP3218349A2 (en) | 2014-11-14 | 2017-09-20 | Gemphire Therapeutics Inc. | Processes and intermediates for preparing , -dicarboxylic acid-terminated dialkane ethers |
| JP6940411B2 (ja) * | 2015-03-13 | 2021-09-29 | エスペリオン・セラピューティクス・インコーポレイテッドＥｓｐｅｒｉｏｎ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | Ｅｔｃ１００２及びエゼチミブを含む固定用量組合せ物及び製剤並びに心血管疾患を処置するか又は心血管疾患のリスクを低減させる方法 |
| MA41793A (fr) * | 2015-03-16 | 2018-01-23 | Esperion Therapeutics Inc | Associations de doses fixes comprenant du etc1002 et une ou plusieurs statines permettant de traiter ou de réduire un risque cardiovasculaire |
| HK1259458A1 (zh) * | 2015-11-06 | 2019-11-29 | Gemphire Therapeutics Inc. | 用於治疗心血管疾病的吉卡宾组合 |
| HK1257556A1 (zh) * | 2016-02-26 | 2019-10-25 | 耀石治疗公司 | 对正接受降脂疗法的纯合型家族性高胆固醇血症患者的治疗 |
| CN110536684A (zh) * | 2017-02-08 | 2019-12-03 | 艾斯柏伦治疗公司 | 三联组合制剂以及治疗心血管疾病或降低心血管疾病风险的方法 |
| JP2020516622A (ja) * | 2017-04-18 | 2020-06-11 | ジェムフィアー セラピューティクス インコーポレイテッド | ゲムカベン、薬学的に許容されるその塩、その組成物、およびその使用方法 |
| TW201906599A (zh) * | 2017-05-11 | 2019-02-16 | 美商珍費爾醫療公司 | 吉卡賓組成物及其使用方法 |
| CN109666727B (zh) * | 2018-12-29 | 2020-11-06 | 中国药科大学 | 一种高活性抑制pcsk9表达的微小rna的用途 |
| AU2020296094B2 (en) | 2019-06-21 | 2025-02-06 | Esperion Therapeutics, Inc. | Methods of making bempedoic acid and compositions of the same |
| CN113134086B (zh) * | 2020-01-20 | 2024-05-24 | 深圳市长卿医学研究院 | 一种降血脂的药物组合物 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5648387A (en) | 1995-03-24 | 1997-07-15 | Warner-Lambert Company | Carboxyalkylethers, formulations, and treatment of vascular diseases |
| US6861555B2 (en) | 2000-01-25 | 2005-03-01 | Warner-Lambert Company | Calcium dicarboxylate ethers, methods of making same, and treatment of vascular disease and diabetes therewith |
| US20020103252A1 (en) | 1997-12-12 | 2002-08-01 | Bisgaier Charles Larry | Statin-carboxyalkylether combinations |
| NZ503982A (en) * | 1997-12-12 | 2002-03-28 | Warner Lambert Co | Statin-carboxyalkylether combinations useful for treating vascular disorders and diabetes mellitus |
| CN1329359C (zh) | 1999-04-01 | 2007-08-01 | 埃斯佩里安医疗公司 | 醚化合物,及其组合物和用途 |
| CN1894195A (zh) | 2000-10-11 | 2007-01-10 | 埃斯佩里安医疗公司 | 用于控制胆固醇以及相关用途的醚化合物以及组合物 |
| US6645170B2 (en) | 2001-03-05 | 2003-11-11 | Bioject Medical Technologies, Inc. | Simplified disposable needle-free injection apparatus and method |
| US20040229954A1 (en) * | 2003-05-16 | 2004-11-18 | Macdougall Diane Elaine | Selective manipulation of triglyceride, HDL and LDL parameters with 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt |
| US7345190B2 (en) | 2003-11-12 | 2008-03-18 | Ssv Therapeutics, Inc. | Carnitine conjugates as dual prodrugs and uses thereof |
| US7579504B2 (en) | 2005-12-07 | 2009-08-25 | Gilead Sciences, Inc. | ABCA1 elevating compounds |
| US8377971B2 (en) * | 2006-08-03 | 2013-02-19 | Trustees Of Tufts College | Non-flushing niacin analogues, and methods of use thereof |
-
2013
- 2013-01-04 CN CN201910123564.7A patent/CN110025608A/zh active Pending
- 2013-01-04 US US14/370,722 patent/US10028926B2/en not_active Expired - Fee Related
- 2013-01-04 MX MX2014008180A patent/MX367352B/es active IP Right Grant
- 2013-01-04 CA CA2861643A patent/CA2861643C/en active Active
- 2013-01-04 CN CN201380004642.2A patent/CN104136023A/zh active Pending
- 2013-01-04 EP EP13733913.1A patent/EP2800564B1/en active Active
- 2013-01-04 JP JP2014551345A patent/JP6295205B2/ja active Active
- 2013-01-04 AU AU2013207423A patent/AU2013207423B2/en not_active Ceased
- 2013-01-04 WO PCT/US2013/020317 patent/WO2013103842A1/en not_active Ceased
- 2013-01-04 HK HK15101958.1A patent/HK1201452A1/xx unknown
- 2013-01-04 EP EP20166700.3A patent/EP3735967A1/en not_active Withdrawn
-
2018
- 2018-02-19 JP JP2018026939A patent/JP2018104452A/ja active Pending
- 2018-06-29 US US16/024,288 patent/US10709678B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN110025608A (zh) | 2019-07-19 |
| AU2013207423B2 (en) | 2017-10-12 |
| US20150005386A1 (en) | 2015-01-01 |
| EP2800564B1 (en) | 2020-05-06 |
| US10028926B2 (en) | 2018-07-24 |
| JP6295205B2 (ja) | 2018-03-14 |
| MX367352B (es) | 2019-08-16 |
| MX2014008180A (es) | 2014-10-14 |
| CN104136023A (zh) | 2014-11-05 |
| JP2015503588A (ja) | 2015-02-02 |
| JP2018104452A (ja) | 2018-07-05 |
| EP2800564A1 (en) | 2014-11-12 |
| US20180303779A1 (en) | 2018-10-25 |
| EP2800564A4 (en) | 2015-07-22 |
| WO2013103842A1 (en) | 2013-07-11 |
| AU2013207423A1 (en) | 2014-07-24 |
| CA2861643A1 (en) | 2013-07-11 |
| HK1201452A1 (en) | 2015-09-04 |
| US10709678B2 (en) | 2020-07-14 |
| EP3735967A1 (en) | 2020-11-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2861643C (en) | Methods of reducing risk of cardiovascular disease | |
| Nikolic et al. | ETC-1002: a future option for lipid disorders? | |
| WO2013136277A1 (en) | Pharmaceutical compositions for treatment of cardiovascular diseases | |
| JP5275975B2 (ja) | 高脂血症の予防及び／又は治療剤 | |
| RU2016129266A (ru) | Композиции и способы лечения и/или предотвращения сердечно-сосудистого заболевания | |
| JP6940411B2 (ja) | Ｅｔｃ１００２及びエゼチミブを含む固定用量組合せ物及び製剤並びに心血管疾患を処置するか又は心血管疾患のリスクを低減させる方法 | |
| EA201390659A1 (ru) | Способы лечения с применением липидных соединений | |
| WO2016181409A1 (en) | Saroglitazar magnesium for the treatment of chylomicronemia syndrome - | |
| JP2009540003A (ja) | Ａａ１ｒａの低頻度投与を含む腎機能の長期間にわたる改善 | |
| JP6207560B2 (ja) | 膵炎を治療するためのゲムカベンおよび誘導体 | |
| JP6650006B2 (ja) | 脂質異常症治療剤 | |
| HK40007806A (en) | Methods of reducing risk of cardiovascular disease | |
| JP2014509305A5 (enExample) | ||
| AU2015202580B2 (en) | Gemcabene and derivatives for treating pancreatitis | |
| Hamilton-Craig | Managing residual risk in patients receiving statin therapy | |
| HK40013864A (en) | Therapeutic agent for dyslipidemia | |
| HK40013864B (en) | Therapeutic agent for dyslipidemia | |
| HK1219662B (zh) | 血脂异常症治疗剂 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20180103 |